: The investigators have cloned a new myelin gene that encodes the Myelin-associated Oligodendrocytic Basic Protein (MOBP). The MOBP gene generates by alternative splicing several small (10kD range) and highly basic (pI>10) intracellular MOBP proteins. MOBP differs from other myelin genes like Myelin Basic Protein (MBP) or Proteolipid Protein (PLP) by structure, by expression only in CNS oligodendrocytes and not in PNS Schwann cells, and by a delayed expression (onset of transcription) during development. The kinetics of the developmental expression of MOBP coincide with the appearance of compact myelin and MNBP in the signaling of myelin sheath compaction. To test this hypothesis they plan to knock-out the Mobp gene and study the development of myelin and the compaction of the myelin sheath as well as to determine the clinical phenotype(s) in such MOBP null mice. They (A. Holz, M.B.A. Oldstone) have recently expressed recombinant MOBP protein and documented that it produced EAE-like disease in SJL/J mice. Several months after this grant was submitted, Maatta et al. (immunology 95:383, 1998) also found that recombinant MOBP protein caused EAE in mice. Thus, two laboratories have documented the encephalitogenic activity of MOBP. Utilizing overlapping MOBP peptides, the investigators mapped the encephalitogenic domain to a single 24 amino acid site. They propose here to map out the precise amino acid residues of MOBP that comprise the encephalitogenic site, perform a detailed immunohistochemical analysis of the CNS lesion(s), generate and characterize T-cells clones from these mice and determine their role and how they cause EAE, and analyze whether MOBP can cause remitting/relapsing demyelinating disease. An area in human MOBP corresponding to the encephalitogenic domain of rodent MOBP fits a HLA DR motif associated with enhanced susceptibility to Multiple Sclerosis (MS). Studies suggested by them and in progress by Roland Martin at the NIH show that lymphocytes taken from patients with remitting/relapsing MS proliferate to selected huMOBP peptide(s). Their studies in rodents combined with those of their collaborator, Dr. Martin, should begin to characterize the role played by MONP in neurologic disease.